research article

Clinical Laboratory and Radiological Findings in COVID-19 Patients with Variable Severity: King Fahad Medical City Experience

Shaeeb Mustafa1, Mohammed Salman Bashir2, Asiya Wali3, Faisal A Alasmari5, Manar A Samman4, Mohammed A AlNamnakani4, Husam Sakkijha1, Abdul Ali Peer-Zada4*

1 Department of Internal Medicine and Pulmonary Intensive Care, KFMC, Riyadh, Saudi Arabia

2 Research Center, KFMC, Riyadh, Saudi Arabia

3 Infection Control and Environmental Health Administration, KFMC, Riyadh, Saudi Arabia

4 Molecular Pathology, Pathology and Clinical Laboratory Medicine Administration, KFMC, Riyadh, Saudi Arabia 5College of Medicine, Al Faisal University, and King Fahad Medical City, Riyadh, Saudi Arabia.

*Corresponding author: Abdul Ali Peer-Zada, Molecular Pathology, Pathology and Clinical Laboratory Medicine Administration, KFMC, Riyadh, Saudi Arabia

Received Date: 09 January, 2023

Accepted Date: 19 January, 2023

Published Date: 24 January, 2023

Citation: Mustafa S, Bashir MS, Wali A, AlAsmari FA, Samman MA, et al. (2023) Clinical Laboratory and Radiological Findings in COVID-19 Patients with Variable Severity: King Fahad Medical City Experience. J Community Med Public Health 7: 280. DOI: https://doi.org/10.29011/2577-2228.100280

Abstract

Background: Patients with Covid-19 infection can present with varying disease severity in the form of critical, severe, and moderate disease. Objectives and Methodology: To assess the significance of clinical laboratory and radiology-based findings in Covid-19 disease severity and their impact on clinical outcome, we performed retrospective analyses using various statistical models, of 412 confirmed Covid-19 patients admitted to our hospital. Results: Descriptive stats revealed 160 critical (38.8%), 153 severe (37.1%) and 99 moderate (24%) cases among 195 Saudi (47.3%) and 217 non-Saudi patients (52.7%) with a mean age of 54 years and male: female ratio of 3.5: 1. Major radiological findings included bilateral air space disease and ground glass opacities with or without consolidation. Overall survival was significantly lower in critical and severe compared with moderate patients (p<0.05). Poor clinical outcome was observed in the elderly and patients with coexisting co-morbidities. NLR is a unique marker and high CRP, ESR, LDH, Ddimer and ferritin levels are independent predictors of disease severity that show strong association with poor outcome in critical and severe Covid-19 patients. Conclusion: Differential Clinical laboratory inflammatory/coagulopathy marker profiles between survivors and non-survivors in Covid-19 patients with variable severity are observed.

Keywords: Coronavirus Covid-19; Acute respiratory distress syndrome; Neutrophil-lymphocyte ratio; C-reactive protein; Lactate dehydrogenase; Erythrocyte sedimentation rate; Shortness of breath

Abbreviations: ARDS: Acute Respiratory Distress Syndrome; NLR: Neutrophil-Lymphocyte Ratio; CRP: C-Reactive Protein; LDH: Lactate Dehydrogenase; ESR: Erythrocyte Sedimentation Rate; SOB: Shortness of Breath

Introduction

Human coronavirus disease, a global public health concern first described in December 2019 and caused by SARS-CoV2 or CoVID-19 manifests with varying degree of signs and symptoms [1,2]. Three major categories of patients with confirmed Covid-19 infection have been recognized: critical patients (~5% of total) requiring life sustaining treatments or procedures, having ARDS, sepsis or septic shock; severe patients (~15% of total) who show signs of pneumonia, severe respiratory distress or oxygen saturation <90%; and non-severe representing both mild and/or moderate cases (~80% of total) who show absence of severe or critical disease signs [3]. Other groups of patients who remain free of any disease during the course of Covid-19 infection called asymptomatic (~17-25%) have also been described [3]. Various factors such as surveillance strategies, therapeutic interventions employed, regional demographics, Covid-19 genotype evolution, and vaccination can be expected to alter Covid-19 severity turnover.

Covid-19 is a highly infectious disease that can lead to fatality. As of January 2023, WHO dashboard (covid19.who.int) shows the number of confirmed deaths reported due to Covid-19 to be 6.8 million globally with a case fatality rate of 0.91%. In Saudi Arabia, the number of deaths due to Covid-19 stands at 9571 (covid19.moh.gov.sa) with a case fatality rate of 1.56%. In China and other countries, a case fatality rate of 4-6% in Covid-19 has been reported [4]. Although vaccination against Covid-19 has had a substantial impact on requirement of hospitalization, disease severity, and mortality rate, uncertainties about their efficacy duration and ‘long Covid-19’ [5] do highlight the need for the identification of better markers for risk stratification, prognostication and effective treatment modalities. Laboratory and radiology-based findings [6,7] could offer an easy and routinely achievable platform to assess predictive markers of disease severity in Covid-19 infection. This study aims to evaluate the significance of laboratory-based inflammatory markers, neutrophil-lymphocyte ratio, and radiological findings among different disease severity groups of COVID-19 patients admitted to a tertiary-care King Fahad Medical City in Riyadh, Saudi Arabia. To our knowledge, this is the first comprehensive laboratory-based investigation from Saudi Arabia and we believe that retrospective analyses are currently a more feasible and practical approach to study laboratory markers in a large cohort of Covid-19 patients.

Methods

Patients

The full cohort of 412 patients included all those admitted to King Fahad Medical City during the peak of pandemic and confirmed by polymerase chain reaction on nasopharyngeal swabs to be Covid-19 positive. Diagnostic criteria and management of patients was done in accordance with WHO and the Ministry of Health, Kingdom of Saudi Arabia guidelines at that time. All the records of the patients PCR results were handled in the Central Command Centre of the Infection Control and Environmental Health department at KFMC. The Departments of PCLMA, Infection Control and KFMC IRB approved the study. Due to the secondary use of data obtained during routine clinical care without any patient contact or harm, informed consent waiver in accordance with IRB policy was obtained.

Routine serial hematologic, biochemical, immunological and/or radiologic investigations were done at KFMC laboratories (CAP accredited). All the data are stored in the hospital management system (EPIC) in individual patient files. Socio-demographic, laboratory and radiologic data were extracted from the medical records and anonymized. Patients were categorized into various disease severity groups in accordance with WHO severity criteria.

Statistical Analysis Procedure

All categorical variables such as gender, age group, nationality, outcomes and severity presented as frequencies and percentages. Continuous variables age, time (days), WBC, Neutrophil, etc. expressed as either Mean ± SD or Median [IQR] depending on the normality of data. The Kolmogorov-Smirnov test was used to confirm the assumption of normal distribution. If the data was biased, a nonparametric test was used. Pearson chi-square / Fisher’s exact test was used to determine significant associations between categorical variables, depending on whether the cell was expected to have an expected frequency of less than 5. One-way ANOVA / Kruskal-Wallis test was used to determine the mean / median significant difference between severity of COVID-19 and factors of the study variables. Overall survival of the patients determined the Kaplan-Meir analysis. A two-sided p-value less than 0.05 was considered statistically significant. All data was entered and analyzed using the SPSS 25 Statistics Package (SPSS Inc., Chicago, Illinois, USA) and MEDCALC software version 20.118.

Results

Patient socio-demographic and clinical characteristics

Table 1 shows the socio-demographic, clinical features and radiological findings of patients based on their categorization into disease severity groups: 160 critical (38.8%) all intubated, 153 severe (37.1%) and 99 moderate (24%) with a mortality of 44%, 19%, and 3%, respectively. Kaplan-Meir analysis of the Overall Survival (OS) showed highly significant lower OS in critical and severe compared with moderate patients (Figure 1a).

 

Figure 1: Lower survival of critical/severe compared with moderate Covid-19 patients: percentage probability survival shown by Kaplan-Meier overall survival (OS) curves over a period of 100 days with a) disease severity, b) gender. The numbers in the bottom show numbers at risk. Percentage survival in disease severity groups with respect to c) different age groups, d) in male and female gender, and e) comorbidity related deaths.

Socio-demographic data and their disease severity distribution shown in Table 1 revealed 195 Saudi (47.3%) and 217 non-Saudi patients (52.7%) with a mean age of 54.7± 14.5 years. Age distribution (<30 to >70 years) revealed majority of the patients over 60 years (44%) and only 19 patients below 30 years (1.3%). Critical (67%) and severe (63%) disease was observed in most patients over 50 years. Gender distribution showed male predominance (77.7% male vs 22.3% females, 3.5:1).

Shortness-Of-Breath, SOB (75.9%), cough (56.8%), fever (49.2%), hypoxia (7%) and chest pain (5%) were major presentation symptoms with the severity distribution shown in Table 1. Other symptoms included viral pneumonia, diarrhea, septic shock, loss of consciousness, tachypnea and only one with known Covid-positive contact.

Variable s

Description

 

Severity

 

Critical (C)

Severe (S)

Moderate (M)

Total

(n = 160)

(n = 153)

(n = 99)

(n = 412)

Intubated

Yes

160 (100.0%)

0 (0.0%)

0 (0.0%)

160 (38.8%)

Outcome**

Survived

89 (56.0%)

123 (80.4%)

95 (96.9%)

307 (74.9%)

Nationality

Saudi

67 (41.9%)

76 (49.7%)

52 (52.5%)

195 (47.3%)

Non-Saudi

93 (58.1%)

77 (50.3%)

47 (47.5%)

217 (52.7%)

Age Group

< 30

9 (5.6%)

5 (3.3%)

5 (5.1%)

19 (1.3%)

30 - 39

11 (6.9%)

16 (10.5%)

13 (13.1%)

40 (2.7%)

40 - 49

32 (20.0%)

37 (24.2%)

22 (22.2%)

91 (6.2%)

50 - 59

38 (23.8%)

46 (30.1%)

21 (21.2%)

105 (7.2%)

 

40 (25%)

29 (18.9%)

24 (24.2%)

93 (22.6%)

30 (18.8%)

20 (13.1%)

14 (14.1%)

64 (15.6%)

Age

Mean ± SD

56 ± 15

54 ± 14

54 ± 16

54.7 ± 14.5

Gender

Male

117 (73.1%)

130 (85.0%)

73 (73.7%)

320 (77.7%)

Female

43 (26.9%)

23 (15.0%)

26 (26.3%)

92 (22.3%)

Symptoms

SOB

124 (77.5%)

120 (78.5%)

69 (69.7%)

313 (75.9%)

Cough

77 (48.1%)

98 (64.1%)

59 (59.5%)

234 (56.8%)

Fever

69 (43.1)

86 (56.2%)

48 (48.5%)

203 (49.2%)

Hypoxia

14 (8.7%)

8 (5.2%)

7 (7.5%)

29 (7%)

Chest pain

3 (1.8%)

8 (5.2%)

10 (10.5%)

21 (5%)

Viral pneumonia

3 (1.8%)

1 (<1%)

0

4 (<1%)

Diarrhea

2 (<1%)

1 (<1%)

6 (6.5%)

9 (2.1%)

Septic shock

2 (<1%)

0

0

2 (<1%)

ARDS

2 (<1%)

0

0

2 (<1%)

Abdominal pain

2 (<1%)

3 (<1%)

3 (3.5%)

8 (2%)

Unconsciousness

2 (<1%)

2 (<1%)

0

4 (<1%)

Hypothermia

1 (<1%)

0

0

1 (<1%)

Tachypnea

0

4 (<1%)

1

5 (<1%)

Sore throat

0

2 (<1%)

0

2 (<1%)

Covid Positive Contact

0

1 (<1%)

0

1 (<1%)

Vomiting

0

3 (<1%)

0

3 (<1%)

Headache

0

0

2 (2.5%)

2 (<1%)

Loss of smell

0

0

1

1 (<1%)

Radiology

Bilateral air space opacities

125 (78.1%)

119 (77.8%)

86 (86.9%)

330 (80.1%)

 

Ground glass opacities with or without consolidation

35 (21.9%)

34 (22.2%)

13 (13.1%)

82 (19.9%)

** highly significant (p<0.05)

 

Table 1: Socio-demographic and clinical characteristics of Covid-19 patients.

Patient Comorbidity Characteristics

Table 2 shows comorbidities appearing in Covid-19 patients among different severity groups. Patients with coexisting cardiac (36.7%) and diabetic (35.4%) comorbidities were more susceptible to critical (47.5% cardiac and 41.3%, diabetes) and severe (39.2% cardiac, 41.2% diabetes) disease. Immunological, neurological or liver and kidney disease and cancer related comorbidities were equally distributed among severity groups (Table 2).

Comorbidities

   

Sev

erity

 

Critical

Severe

 

Moderate

Total

(n = 160)

(n = 153)

 

(n = 99)

(n = 412)

Cardiac disease

76 (47.5%)

60 (39.2%)

 

15 (15.2%)

151 (36.7%)

Diabetes mellitus

66 (41.3%)

63 (41.2%)

 

17 (17.2%)

146 (35.4%)

Immune disease

12 (7.5%)

5 (3.2%)

 

13 (13.1%)

30 (7.3%)

Kidney disease

8 (5%)

5 (3.2%)

 

6 (6.6%)

19 (4.6%)

Cancer

5 (3.1%)

1 (<1%)

 

4 (4.4%)

10 (2.4%)

Neurological disease

2 (1.3%)

4 (2.6%)

 

3 (3.3%)

9 (2.2%)

Liver disease

2 (1.3%)

1 (<1%)

 

0

3 (<1%)

   

Co-morbidities related deaths

   

Cardiac disease

39 (51.3%)

17 (28.3%)

 

1 (6.7%)

57 (37.7%)

Diabetes mellitus

38 (57.5%)

15 (23.8%)

 

0

53 (36.3%)

Immune disease

5 (41.7%)

2 (40%)

 

0

7 (23.3%)

Kidney disease

7 (87.5%)

5 (100%)

 

0

12 (63.2%)

Cancer

4 (32%)

1 (100%)

 

0

5 (50%)

Neurological disease

0

1 (25%)

 

1 (33%)

2 (23%)

Liver disease

1 (50%)

1 (100%)

 

0

2 (66.7%)

Table 2: Co-morbidities distribution and clinical outcome of Covid-19 patients.

Clinical Laboratory Characteristics

Neutrophil-Lymphocyte Ratio (NLR): We collected clinical laboratory data at the time of admission for hematology markers: total and differential White Blood Count (WBC), neutrophil and lymphocyte counts, NLR;biochemical inflammatory markers: CRP, ESR, LDH, and ferritin;coagulation markers: Ddimer, APTT and INR; liver enzyme levels: ALT and AST and cardiac marker troponin levels (Table 3, Figure 2). Neutrophilia and lymphopenia at presentation was a consistent observation most notable in critical and severe Covid-19 patients analyzed in this study. The mean ±SD neutrophil count (reference range 30-70%) was 81.5 ± 9.4, 80.3 ± 9.1, and 76.3 ± 11.7, and mean lymphocyte count (reference range 23-60%) was 12.1 ± 7.6, 12.6 ± 7.1, and 15.6 ± 8.7 in critical, severe and moderate patients on admission, respectively. We calculated NLR due to its good predictive value on disease severity and mortality in Covid-19 patients, and observed significantly elevated NLR [Median (IQR)] on admission in critical [11.4 (14.7-4.6)], in severe [10.1 (10.9-4.8)] and in moderate [7.1 (8.7-3.4)] cases (p<0.05).

 

Figure 2: Higher mean laboratory marker levels at presentation in each disease severity group of Covid-19 patients: marker levels on admission for listed analytes. Reference ranges are given in the text and all values are above the range.

Inflammatory markers: On admission we observed increased ESR (reference range 0-20) in critical (60.5 ± 32.3), in severe (59.8 ± 27.9), and in moderate (78.9 ± 31.5) cases; increased CRP (reference range 1-3 mg/L) in critical [126 (193.7-68.2)], in severe [121 (165.7-76.2)], and in moderate [112.5 (171-64.1)] cases; increased LDH (reference range 125-220 U/L) in critical [677 (881-530)], in severe [649 (872512)], and in moderate [555 (700.5-401.5)] cases; increased ferritin (reference range (10-204 ng/mL) in critical [1149.2 (2406.9-522)], in severe [1042.9 (2213.2-572.1)], and in moderate [729.6 (1664.1-349.5)] cases (Table 3, Figure 2).

Marker on admission

Description

Severity

 

P -

value

Critical

Severe

Moderate

WBC

Median [IQR]

10.2 [14.6 - 6.7]

8.7 [11.3 - 6.2]

7.1 [10.1 - 5.4]

* 0.001

Neutrophil

Mean ± SD

81.52 ± 9.43

80.33 ± 9.12

76.34 ± 11.76

* <0.001

Lymphocyte

Mean ± SD

12.03 ± 7.64

12.56 ± 7.06

15.59 ± 8.74

* 0.001

NLR

Median [IQR]

7.3 [14.76 - 4.66]

7.14 [10.99 - 4.88]

5.86 [8.72 - 3.47]

* 0.002

CRP

Median [IQR]

126 [193.75 - 68.18]

121 [165.75 - 76.23]

112.5 [171 - 64.08]

0.546

ESR

Mean ± SD

60.49 ± 32.36

59.81 ± 27.91

78.86 ± 31.48

* 0.027

LDH

Median [IQR]

677 [881 - 530]

649 [872 - 512]

555 [700.5 - 401.5]

* <0.001

Ferritin

Median [IQR]

1149.2 [2406.9 - 522]

1042.95 [2213.23 - 572.03]

729.6 [1664.1 - 349.5]

* 0.011

Ddimer

Median [IQR]

1.62 [5.03 - 0.78]

1.07 [1.98 - 0.64]

0.85 [1.74 - 0.46]

* <0.001

INR

Mean ± SD

1.22 ± 0.19

1.22 ± 0.2

1.22 ± 0.33

0.938

APTT

Mean ± SD

33.38 ± 15.75

31.45 ± 4.78

31.56 ± 3.92

0.202

AST

Median [IQR]

56 [84.5 - 39.5]

56 [85.5 - 39]

47 [64 - 29]

* 0.005

ALT

Median [IQR]

36 [65 - 25]

43 [69 - 30]

35 [60.5 - 22.5]

0.103

Troponin

Median [IQR]

20.7 [94.93 - 6.7]

10.1 [34.05 - 5]

7.4 [16.9 - 4]

* <0.001

Table 3: Laboratory marker distribution in Covid-19 disease severity.

Coagulopathy markers: On admission we observed increased Ddimer (reference range 0-0.5 µg/mL) in critical [1.6 (5.1-0.78)], in severe [1.1 (1.98-0.64)], and in moderate [0.85 (1.74-0.46)] cases; normal APTT (reference range 25.3-38.3 s) in critical 33.4 ± 15.8, in severe 31.5 ± 4.8, and in moderate 31.6 ± 3.9 cases; normal INR (reference range 0.8-1.23 N) in critical 1.2 ± 0.19, in severe 1.22 ± 0.2, and in moderate 1.22 ± 0.33 cases (Table 3, Figure 2).

Liver enzymes and cardiac disease markers: On admission (Table 3, Figure 2) we observed increased AST (reference range 5-34 U/L) in critical [56 (84.5-39.5)], in severe [56 (85.5-39)], and in moderate [47 (64-29)] cases; normal ALT (reference range 0-55 U/L) in critical [36 (65-24)], in severe [43 (69-30)], and in moderate [35 (60.5-22.5)] cases; increased troponin (reference range 0-15.6 ng/L) in only critical cases [20.7 (94.9-6.7)].

Clinical Outcome

The clinical outcome of patients in the form survival (discharge form hospital) or death among disease severity groups is shown with respect to age (Figure 1c), gender (Figure 1d) and comorbidity distribution (Figure 1e). The clinical outcome in relation to various laboratory markers described above is shown (Table 4, Figure 3). The data revealed decreasing survival with increasing age in critical and severe patients (Figure 1c). Majority of the moderate patients survived in all age groups. Survival in females was comparatively lower with more deaths than males but not statistically significant (Figure 1b, 1d). Comorbidities were associated with poor clinical outcome (Table 3). More than half of the critical patients with coexisting cardiac disease and diabetes mellitus did not survive. Fatality was comparatively lesser in severe and moderate patients with these comorbidities (Figure 1e). In moderate patients with a total of three deaths, two had coexisting comorbidities (Table 3, Figure 1e) and the other with age >70 (Table 2, Figure 1c). Critical and severe patients with very high levels of NLR, CRP, LDH, ferritin, and Ddimer had very poor outcome and died than those with normalized values, who survived (Figure 3) suggesting a high predictive value of these markers in Covid-19 infection. It is interesting to note that while elevated ESR was observed on admission among different severity groups, but there was no significant effect on the clinical outcome (Figure 3, ESR panel).